N-aryl-3-cyano-4,6-dimethylpyrid-2-ones



United 3,503,986 Patented Mar. 31, 1970 3,503,986 N-ARYL-3-CYANO-4,6-DIMETHYLPYRID-2-ONES Michael C. Seidel, Levittown, Kenneth L. Viste, Warminster, and Roy Y. Yih, Doylestown, Pa., assignors to Rohm and Haas Company, Philadelphia, Pa., a corporation of Delaware No Drawing. Filed Jan. 16, 1968, Ser. No. 698,106 Int. Cl. C07d 29/42; A01n 9/22 US. Cl. 260-2943 3 Claims ABSTRACT OF THE DISCLOSURE Novel compounds belonging to the class of N-arylpyrid-2-one-4,6-dimethyl-3-carboxylic acids and their amides, esters and salts. These compounds possess biological activity and in particular are plant growth regulators. Novel N aryl-3-cyano-4,6-dimethylpyrid-2-oues are also disclosed.

This invention is concerned with new organic compounds belonging to the general class of N-arylpyrid-2- ones. It also relates to the biological activity of these structures. In particular they are useful for influencing the growth and development of plants in various ways as will be more fully developed hereinafter.

These new structures may be depicted by the general formula OH I 3 wherein Y is selected from the group consisting of NH and OR Where R is chosen from the group consisting of hydrogen, alkyl groups of 1 to 4 carbon atoms and a saltforming cation,

X is selected from the group consisting of amino, fiuoro,

chloro, bromo, iodo, methyl, methoxy and nitro,

X is selected from the group consisting of fiuoro, chloro,

bromo, iodo, methyl and methoxy,

n is 0,1, or 2, and

X may be hydrogen when n is l or 2 and X is at least one halogen in the 3-position.

1- 4-methylphenyl) -3 -carboxy-4,6-dimethylpyrid-2-one 1- 4-methoxyphenyl) -3-carboxy-4,6-dimethylpyri-d-2-one 1- (2,4-dichlorophenyl) -3-carboXy-4,6-dimethylpyrid- 2-one 1- (2,4-dibromophenyl) -3 -carboxy-4, G-dimethylpyrid- Z-one 1- (2-methyl-4-chlorophenyl) -3 -carboxy-4,6-dimethylpyrid-2-one 1-(2-chloro-4-methylpheny1)-3-carboXy-4,6-dimethylpyrid-Z-one 1- 2-methoxy-4-bromophenyl) -3 -carboxy-4,6-dimethylpyrid-Z-one 1- (2-fluoro-4-chlorophenyl -3-carboxy-4,6-dimethylpyrid-Z-one 1- (3-fluoro-4-chlorophenyl -3-carboxy-4,6-dimethylpyrid-2-one 1- (3 ,4-dichlorophenyl) -3-carboxy-4,6-dimethylpyrid- 2-one 1- 3-chloro-4-bromophenyl -3-carboxy-4,6-dimethy1- pyrid-2-one 1- (3 (chloro-4-methylphenyl) -3-carboxy-4,6-dimethylpyrid-2-one 1- (4-chloro-3-methylphenyl)-3-carboxy-4,6-dimethylpyrid-Z-one l- 3-methyl-4-methoxyphenyl) -3-carboxy-4,6-dimethylpyrid-2-one 1- (3 ,4-dimethylphenyl) -3 -carb oXy-4,6-dimethylpyrid- 2-one 1- (3 -chloro-4-methoxypheny1) -3 -carb oXy-4,6-dimethylpyrid-Z-one 1- (3 -chloro-4-nitrophenyl) -3-carboxy-4,6-dimethylpyrid-2-one 1- (2,3 ,4-trichlorophenyl) -3 -carboXy-4,6-dimethylpyrid- 2-one 1- 2,4,6-trichloropheny1) -3 -carboXy-4,G-dimethylpyrid- 2-one 1- (2-methyl-3,4-dichlorophenyl) -3-carboXy-4,6-dimethylpyrid-2-one 1- 4-methyl-2,3-dichlorophenyl) -3 -carboxy-4,6-dimethylpyrid-2-one 1- (4-methyl-2-ch1oro-6-fluorophenyl) -3-carb0-Xy-4,6-dimethylpyrid-Z-one and salts of the above.

1- 3-iodophenyl) -3-carbamyl-4,6-dimethylpyrid-2-one 1- (4-methylphenyl) -3 -carb amyl-4,6-dimethylpyrid-2-one 1-(4-methoxypheny1) -3 -carb amyl-4,6-dimethylpyrid-2- one 1- 4-bromophenyl) -3 -carbamyl-4,G-dimethylpyrid-Z-one 1 4-chlorophenyl) -3 -carbamyl-4,6-dimethylpyrid-2-one 1- (2,4-dichlorophenyl -3 -carbamyl-4,G-dimethylpyrid- 2-one 1- 2,4-dimethylphenyl -3 -carb amyl-4, G-dimethylpyrid- 2-one 1- 2-bromo-4-methylphenyl) -3 -carb amyl-4,6-dimethylpyrid-Z-one 1- 2-bromo-4-fluorophenyl) -3-carbamyl-4,6-dimethylpyrid-Z-one 1- (3 -methyl-4-fiuorophenyl) -3 -carbamyl-4,6-dimethylpyrid-Z-one 1- 3,4-dichlorophenyl) -3-carbamyl-4,6-dimethylpyrid- 2-one l- (3 ,4-dimethylphenyl) -3 -carbamyl-4,6-dimethylpyrid- 2-one 1- (3 ,4-dimethoxyphenyl) -3-carbamyl-4,6-dimethylpyrid- 2-one 1- 3,4-dibromophenyl) -3-carbamyl-4,6-dimethylpyrid- 2-one 1- (3,4-difluorophenyl) -3 -carbamyl-4,6-dimethylpyrid 2-one 1- (3-chloro-4-methoxyphenyl) -3 -carbamyl-4,6-dimethy1- pyrid-Z-one Based on plant growth regulatory activity, preferred compounds of this invention include 1-(4-chlorophenyl) 3-carboxy-4,6-dimethylpyrid 2 one, 1-(3,4-dichlorophenyl) 3 carboxy-4,6-dimethylpyrid-2-one and their water-soluble salts.

Water soluble salts of the compounds of this invention where Y of Formula I is OH include the alkali metal salts, preferably the sodium and potassium; the ammonium; mono, di and trialkylammonium wherein each alkyl group may contain up to 4 carbon atoms, preferably methylammonium, dimethylarnmonium, trimethylammonium and triethylammonium; ethanolamine and propanol amine salts such as the Z-hydroxyethylammonium, 2-hydroxypropylammonium, bis(2-hydroxyethyl)ammonium and tris(2-hydroxyethyl)ammonium; andquaternary ammonium salts such as tetramethylammonium and choline. Other useful salts include the alkaline earth salts, particularly the calcium and magnesium, aluminum, cadmium, copper ferric, ferrous, manganese, nickel and zinc.

The compounds of this invention may be prepared by hydrolysis of 1-aryl-3-cyano-4,6-dimethylpyrid-2-ones corresponding to the formula;

Partial hydrolysis of the -CN group to --CONH results in the 1-aryl-3-car bamyl-4,6-dimethylpyrid-2-ones and complete hydrolysis gives 1-aryl-3-carboxy-4,6-dimethylpyrid-Z-ones. In many instances hydrolysis results in a mixture of the 3-carbamyl and 3-carboxy derivatives and these may be separated by conventional means such as by converting the 3-carboxy derivative to a watersoluble salt and removing the insoluble 3-carbamyl derivative. The reaction mixture consisting essentially of the two types of hydrolysis products with generally a minor amount of the unreacted cyano precursor can be used for biological purposes directly without separation. Tests on the cyano precursor have shown that it neither has biological activity nor does it interfer with the biological activity of the hydrolysis products.

The 1-aryl-3-cyano-4,6-dimethylpyrid-2-ones (Formula II) may be prepared by condensation of pentane-2,4- dione(acetylacetone) with cyanoacetanilides of the formula:

NCCHzQ ONE- (III) in the presence of a basic catalyst. The reaction may be depicted as follows using the mono-enol form of pentane-2,4-di0ne.

CH3 CN /C=O H2O HO =0 II Formula II /O\ HIII catalyst H30 OH Pentane-2,4-dione is a product of commerce.

cyanoacetanilides are known compounds which may be made by heating ethyl cyanoacetate with the appropriate aniline, usually under neat conditions, and removing the ethanol as formed according to the reaction:

NCCHZCO O C 11 H2N- Formula III 0 11 011 This is usually a facile reaction in the temperature range of ISO-250 C. The end of the reaction is judged when the removal of ethanol is essentially complete. The reaction product may be purified by standard means, such as recrystallization, or may be used without further purification. Refer to Piccinini et al. Chemisches Zentralblatt 78, 335 (1907).

In the condensation of pentane-2,4-dione with a cyanoacetanilide equimolar amounts of the two reactants are normally used, although excesses of either reagent are permissible. In some instances, it may be expedient to use an excess of pentane-2,4-dione.

The condensation of pentane-2,4-dione with a cyanoacetanilide is preferably carried out in the presence of a solvent. Suitable solvents include alcohols, ethers, aliphatic hydrocarbons, aromatic hydrocarbons, dimethylformamide, dimethyl sulfoxide and carbon tetrachloride. The preferred solvents are the alcohols such as methanol, ethanol, isopropanol and mono-ethers of ethylene glycol. Heat is required for the condensation and this is usually obtained at the reflux temperature of the solvent used. Temperatures in the range of 50 to C. are suitable.

The condensation of pentane-2,4-dione with a cyanoacetanilide is catalyzed by basic catalysts. Typical catalysts include inorganic bases, amines and quaternary ammonium hydroxides. Amine catalysts are preferred and good results have beenobtained with piperidine, pyridine, diethylamine and triethylamine for example. General conditions for this type of condensation are reviewed in Heterocyclic Compounds, edited by A. Weissberger, Interscience Publishers, 1962, in Part III on Pyridine and Derivatives, Chapter 12 by H. Meislich on Pyridinols and Pyridones, pp. 525-531.

The 1-aryl-3-cyano-4,6-dimethylpyrid-2-ones can also be prepared by the general method described in the above cited book Heterocyclic Compounds on p. 569. This consists of quaternizing 3-cyano-4,6-dimethylpyridine with an iodobenzene of the structure in a solvent having a high dielectric constant, such as acetonitrile, and oxidizing the resulting pyridinium salt with alkaline potassium ferricyanide to the corresponding u-pyridone. The reaction may be depicted as follows:

E i r -CN CN )n CH3 CH3 \N I i l X V) K Fe(CN)a, alkali Formula IV Formula II The 1-aryl-3-cyano-4,6-dimethylpyrid-2-ones may also be prepared by a ring-closure procedure generally described in the above cited book Heterocyclic Compounds at pp. 540-541. By this procedure acetone is condensed with a fi-ketoamide of the type in the presence of polyphosphoric acid to give compounds of Formula II.

1 aryl 3 a1koxycarbonyl-4,6-dimethylpyrid-2-ones may be prepared from a substituted a-pyrone according to the general procedure described in the above cited book Heterocyclic Compounds on page 551. The reaction may be depicted for the 3-methoxycarbonyl compounds as follows:

The compounds of Formula V may be converted to the corresponding carboxy compounds or their Water-soluble salts by standard hydrolytic procedures.

The hydrolysis of 1-aryl-3-cyano-4,6-pyrid-2-ones may be exemplified by the following reaction sequence:

l ON H20 momma CH3 T o on, f 0

x')n @AX) The hydrolysis of the nitrile (Formula II) proceeds to either the amide (Formula VI) or the acid (Formula VII) under acidic or alkaline conditions. Aqueous organic and mineral acids are suitable for this purpose. Typical of such acids are formic, acetic, hydrochloric, sulfuric and phosphoric. The temperature requirements for the hydrolysis are such that the temperature must be high enough to allow the hydrolysis to proceed but not sufficiently high to cause decarboxylation. This is normally in the range of 50 to 150 C., with a preferred range of to 120 C. When alkaline conditions are used for the hydrolysis this is usually with strong aqueous alkalies such as sodium and potassium hydroxide. The cyano compounds of Formula II can be converted to the carbamyl derivatives of Formula VI by hydrolysis with hydrogen peroxide in dilute base. The carbamyl derivatives can be hydrolyzed to the free acids of Formula VI by means of nitrous acid. Typical hydrolytic conditions are well known in the chemical art.

The acids of Formula VII are readily converted to derivatives. For example, direct esterification with alcohols gives esters and reaction with halogenating agents such as thionyl chloride or bromide and phosphorus pentachloride gives the acid halides. The acid halides can in turn be converted to esters, amides, anilides and other common derivatives by standard procedures.

The following examples are illustrative of preparations of the compounds of the invention, but are not to be construed as limitations thereof. The example numbers correspond to those given in subsequent Table III, IV and V.

EXAMPLE 1 Preparation of 1-(4-chlorophenyl)-3-carboxy-4,6- dimethylpyrid-Z-one (a) 1 (4 chlorophenyl)-3-cyano-4,6-dimethylpyrid-Z- arm-A reaction mixture consisting of 19.4 g. (0.1 mole) of p-chlorophenylcyanoacetanilide, 10 g. (0.1 mole) of pentane-2,4-dione, 5 ml. of piperidine and 200 cc. of ethanol was refluxed for 3 hours. The reaction mixture was cooled to give a solid which was filtered off, Washed with methanol and recrystallized from glacial acetic acid to give 22 g. of crystals. This white solid melted at 314- 316 C. It was found by analysis to contain 64.96% C, 4.25% H and 10.76% N; calculated for C H ClN O (molecular weight, 258.7) is 64.99% C, 4.29% H and 10.83% N. It is an 83% yield of l-(4-chlorophenyl)-3- cyano-4,6-dimethylpyrid-Z-one.

(b) 1 l-chlorophenyl)-3-carb0xy-4,6-dimethylpyrid- 2-one.Forty grams (0.155 mole) of 1- (4-chlorophenyl)- 3-cyano-4,6-dimethylpyrid-Z-one was dissolved in a solution of ml. of concentrated sulfuric acid in 60' ml. of Water. The reaction mixture was heated on a steam bath over night. After cooling the product was poured into water to give a solid which was filtered ofl? and recrystal lized from ethanol. The isolated solid was 22.5 g. of white solid which melted at 2l5217 C. This was found to contain by analysis 60.60% C, 4.27% H and 5.10% N; calculated for C H ClNO (molecular weight, 277.7) is 60.55% C, 4.36% H and 5.05% N. The product is a 52% yield of 1-(4-ch1orophenyl)-3-carboxy-4,6-dimethylpyrid-Z-one.

7 EXAMPLE 12 Preparation of 1-(4-chlorophenyl)-3-carbamyl-4,6- dimethylpyrid-2-one A reaction mixture consisting of 777 g. (3 moles) of 253-255 C. The product is a quantitative yield of the sodium salt of 1-(3,4-dichlorophenyl)-3-carboxy-4,6-dimethylpyrid-2-one. I

The sodium salt of 1-(4-chlorophenyl)-3-carboxy-4-,6

dimethylpyrid-Z-one (Example 20) was prepared in the 1 r p y y y1py n same way. The recrystallized solid was found to be 95.7% 1940 ml. of concentrated sulfuric acid and 1164 m1. of ure by titration and melted at 270-272" C. water was heated on a steam bath at 90-95 C. for 15 EXAMPLE 24 hours. The cooled mixture was poured into 7 l. of water and the resulting solid was filtered 011. The solid was 1 1 treated with 1600 g. of 25% aqueous sodium hydroxide, 10 gg gi igg iigg$ggiiggg filtered and the solid residue treated with 2200 g. of 10% aqueous sodium hydroxide with stirring for 4 hours at room temperature. The product was filtered and from the z g i of 'g 3 3 filtrate there Was isolated 326 g. (a 39% yield) of 1- 4- 15 6 chlorophenyl)-3-carboXy-4,6-dimethylpyrid-2-one. The inmet an m 0 concen ta 6 soluble residue, which was 257 g. of solid melting at 206- hydrochlonc acid was Smred at reflux tempiarature C. was washed with 1000 g. of 10% aqueous Sodium about 16 hours. It was cooled to 10 to give a whlte hydroxide then with water, filtered and the residue dried sohd was filteged washed F 9 methanol to give 250 g. of almost white solid melting at 211- 20 The P uct was 8 o a 1g t tan crys' 213 C. By NMR this was shown to be essentially 1-(4- talllne solid melting at 188-189 C. Infrared spectroschlorophenyl) 3 carbamyl 4g6 dimethy1pyrid 2 0ne and as copy confirmed that the product was exclus vely an ester. such is a 30% yield. A sample of the solid was recrystal- The Sohd was found to contam by analysls 61,7192 lized from a 50:50 mixture of acetone-methanol to give 470% 12'58% f- N and 0; the product as a white crystalline solid melting at 222- culated for C15H14CINO3 15 61-75% 434% H 12'17% 226 C. This solid was found to contain by analysis Q 430% N and 16-44% The Product 15 a 61.71% C, 476% H, 12 65% C1, 10 01% N and yleld of 1-(4-chlorophenyl)-3-methoxycarbonyl-4,6-dl- 11.39% 0; calculated for c clis o (molecular methylpynd-l-oneweight, 276.7) 60.76% C, 4.73% H, 12.82% Cl, 10.13% TABLE 1 N and EXAMPLE 21 Preparation of cyanoacetanilides Preparation of the sodium salt of 1-(3,4-dichlorophenyl)- Preparatlon: Nfemng p 01m 3-carboxy-4,6-dimethylpyrid-2-one X To a solution of 177.5 g. of 50.2% aqueous sodium NCCHzC(O)NH-X hydroxide (2.2 moles) in 3800 g. of deionized water was I added 722 g. of 96% 1-(3,4-dichlorophenyl)-3-carboxy- 4-chloro-2-cyanoacetanilide 201-203 4,6-dimethylpyrid-2-one (2.22 moles). This was stirred 4'-methyl-2-cyanoacetanilide 186-187 until solution resulted. The solution was poured onto 4-methoxy-2-cyanoacetanilide 134-135 trays and the water allowed to evaporate to give a solid 40 4'-nitro-2-cyanoacetanilide 198-202 which Was then dried in a forced-draft oven at about 50 3'-fiuoro-2-cyanoacetanilide 163-165 C. for 4 hours. There was obtained 872 g. of a dry tan- 3'-chloro-2-cyanoacetanilide 131-134 colored powder which melted with decomposition at 2',4-dichloro-2-cyanoacetanilide 118-123 244 C. Analysis showed it to contain 17.5% water. Mass 3,4-dichloro-2-cyanoacetanilide 161-164 spectrographic analysis indicated homogenity. The product 3'-fluoro-4'-methyl-2-cyanoacetanilide 178-180 was recrystallized from water. Titration with 0.5 N hydro- 3'-chloro-4'-methyl-2-cyanoacetanilide 149-151 chloric acid showed it to be 96% pure. It melted at 3',4'-dimethyl-2-cyanoacetanilide 138-140 TABLE II Preparations of 1-aryl-3-cyallo-4,G-dimethylpyrid-Z-ones Melting Empirical Analysis Preparation Point 0.) Formula Element Found Calculate 1-(4-ehlorophenyl)-3-cyano-4,6-dimethy1py i -2-0 4-316 C1lHllC1N2O 75.35 75.65 1-(4-methylphenyl)-3-cyauo-4,6-dimethy1py1id2-0 16 274-276 CnsHnNzO 5.77 5.92 11.71 11.75 7.21 6. 72

1-(4-metl1oxyphenyl)-3-cyano-4,6,-dimet1lylpyrid-2-one 247-249 CmHmNzOz 70.30 70.85

ii. 1% li'. 12.77 12.58

1-(4-nitrophenyl)-3-cya11o-4,6-dimethylpryid-2-0ne 278-281 OnHnNaoe 62.42 62.49 H 4.03 4.12 N 15. 91 15. 53 0 17. 59 17. 84

1-(3-fluoropheny1)-3-cyano-4,6-dimethyIpyrid-2-one 287-289 CnHnFNtO C 9, 3 9,40 H 4.76 4. 58 N. 11.70 11.57

TABLE II-Continued Analysis Meltin Empirical Preparation Point C. Formula. Element Found Calculated 1-(3-ch1orophenyl)-3-cyano-4,6-dimethy1pyr1d-2-one 249-250 CnHuClNzO 62. 62. 3g 13: 50 13'. 70 10. 76 10. 82 6. 58 6. 20

1-(2,4-dieh1oropheny1)-3-cyano-4,6-dimethy1py1'id-2-one 222-224 01411100129120 5g- 1-(3,4-d1oh1orophenyl)-3-cyano-4,6-dimethy1pytid-2-one 278-27 9 CuHmChNzo 537. 53g 5;. 231 70 24120 9. 46 9. 55 5. 75 5. 47

1-(3-fluoro-4-methy1phenyl)-3-cyano-4,6-dimethy1pyrid-2-one 306-308 C1sH1oFN2O 7:. 212 721.3(7) 111 13 11: 07

1-(3-ehloro-4-methylphenyl) -3-cyano-4,6-dimethy1pyrid-2-one 259-260 015H1aClN 62. g1); 62. 131 09 13'. 00 10. 24 10. 27 6. 43 5. 86 I-(3,4-dimethylpheny1)-3-cyano-4,cyano,6-dimethy1pyrid-2-one 255-257 C15Hl6N20 7g. 2g 7g. 11: 23 11: 11 6. 64 6. 34

TAB LE III Examples of 1-ary1-3-carboxy-4,fi-dimethylpyrid-il-ones 1 .0 O O H CH3 J 0 \N Analysis Melting Empirical Example X X Point 0.) Formula Element Found Calculated H 215-217 C 4H 2C1NO3 70. 26 70. 05 11 183-185 C15H15N0a 5. 94 5. 88 5. 64 5. 45 18. 68 18. 68

H 217-220 CI6HIENO4 66. 27 66. 00 5. 63 5. 34 5. 33 5. 13 23. 23.

4 N02 H 237-240 014Y12N205 5761 58. 33 4. 20 4. 19 11. 03 9. 72 25. 43 22. 75

5 H 3-]? 239-240 C14H12FNO3 64. 46 64. 36 5. 00 4. 63 7. 29 7. 27 5. 35 5. 36

6 H 3-01 226-228 CHHmCINOa 60. 49 60. 4. 39 4. 35 13. 03 12. 77 5. 05 5. 04 17. 58 17. 28

7- 01 2-01 153-155 014H11C12NO5 54. 35 53. 85 3. 87 3. 55 22. 23 22. 72 4. 95 4. 48 13. 75 15. 40

8 01 3-01 240-242 CuHgClzNOs 52. 47 53.85 3. 3. 55 21. 68 22. 72 4. 51 4. 48 15. 38 15. 40

9 0H3 3-F 233-234 C1 H1 FNO3 65. 57 65. 45 5. 30 5. 13 6. 87 6. 90 5. 15 5. 09

10 0113 3-01 229-231 ClaHuClNOa 61. 45 61. 75 4. 66 4. 83 12. 44 12. 15 4.83 4. 16. 05 16. 45

H 208-210 C H N0 70. 81 70. 85 11 CH3 3 C s 10 17 a 6.49 6.32 5. 28 5. 17 17. 54 17. 22

TABLE IV Examples of 1-ary1-3-carbamyl-4,fi-dlmethylpyrid-Z-oncs r CONHz CH LO Analysis Melting Empirical Example X X Point 0.) Formula Element Found Calculated 12 C1 H 222-226 CuHiaClNzOz I 13.. CH3 H 225*229 CisHmNzOz 70. 62 70. 35 6. 36 6. 30 10. 10. 93 13. 51 12. 50

14 N 02 H 210-212 GHHISNSOA 56.82 58. 53 4. 48 4. 56 14. O4 14. 63 22. 33 22. 29

15 H B-F 212222 CmNmFNzOz 64. 66 64. 58 (dec.) 5. 00 5. 03 7. 24 7. 10. 76 10. 76

16- H 3-01 207220 CuHraClNzOz 60.90 60. 76 (dec.) 4. 76 4. 74 13. 26 12. 81 9. 83 10. 12 11. 2O 11. 56

17 C1 2-Cl 197-199 CuHnClzNzOz 55. 02 54. 04 4. 00 3. 89 22. 70 22. 79 7. 59 9. O0 10. 16 10. 28

18 CH 3-F 219-221 CIEHIEFNZOZ 65.77 65. 68 5. 5. 51 6. 84 6. 93 10. 1O 10. 21

19 CH 3-0113 243-245 CmHrsNzOz 71. 20 71.00 6. 6. 73 9. 90 10. 38 12. 19 11. 86

TABLE V 5 tained. Individual plant species give different types of Examples of Derivatives of l-aryl-3-carboxy-4,6-

dimethylpyrid-Z-ones Examples:

20 Sodium salt of l-(4-chlorophenyl)-3-carboxy- 4,6-dimethylpyrid-2-one.

21 Sodium salt of 1- (3,4-dichlorophenyl)-3-carboxy-4,6-dimethylpyrid-2-one.

22 Dimethylamine salt of l-(4-chlorophenyl)-3- carboxy-4,6-dimethylpyrid-2-one.

23 Dimethylamine salts of l-(3,4-dichlorophenyl- 3-carboXy-4,6-dimethylpyrid-2-one.

24 1 (4-chlorophenyl)3-methoxycarbonyl-4,6-dimethylpyrid-Z-one.

The compounds of this invention have been found to produce a variety of plant responses. These responses are observed when the compounds alone or in a carrier or as formulations are applied to the plant itself, as by foliar application, or to plant parts such as by seed treatment or to the environment or habitat of the plant, such as by soil drenching or soil incorporation. The most outstanding plant-growth influencing property observed is suppression of growth. This is most commonly found to a growth inhibitory action on the stern, i.e. stem elongation is inhibited. In other instances flowering or seed formation is altered. In other cases malformation of leaves is noted. Sometimes, particularly at high dosages, a plant species may be herbicidally sensitive.

Pre-ernergence herbicidal activity has also been obresponses and any one or several of these plant responses may be observed for any given species. The major contribution of the compounds of this invention to the field of plant growth regulation is that they provide non-injurious plant growth regulants which inhibit stem elongation of many weed, crop and woody species and alter flowering and fruit development.

A soil drench test was used as one method for evaluating the plant growth regulating properties of the compounds of this invention. In this test, seeds or plants were planted in pots and at a given stage of growth the soil was watered with a preparation containing the compound at given dosages in terms of pounds per acre. Growth responses were subsequently observed.

In one such test about 20 wheat seeds were planted in a 4 inch pot and allowed to grow for 11 days, at which time the second leaf of wheat was emerging. A solution or suspension of the chemical was prepared by dissolving the compound in about 1 ml. of acetone or water and adding sufiicient water to make 50 ml. The amount of chemical was such as to provide 2 and 20 pounds per acre. For example 2 mg. give 2 lbs./A or 2.2 kilos per hectare. Each test was run in triplicate and untreated plants were included as controls. Four weeks after treatment the overall height of the plants from the soil level to the leaf tip was measured.- The percent inhibition was calculated as height of treated plant TABLE VI Inhibition of Wheat Plants by Soil Drench Percent Inhibition at Example 2lbs./A 20lbs./A

1 Data two weeks after treatment.

In this type of test the following compounds gave no inhibition of wheat plants, i.e. the plants were similar to untreated controls.

1-phenyl-3-carboxy-4,6-dirnethylpyrid-2-one l-phenyl-3-carbamyl-4,6-dimethylpyrid-2-one 1- (2-chlorophenyl) -3-carb oxy-4,6-dimethylpy1id-2-one l-(4-chlorophenyl)-3-cyano-4,6-dimethylpyrid-2-one l-(3,4-dichlorophenyl)-3-cyano-4,6-dimethylpyrid-2-one For foliage spray tests, the compounds were dissolved in an appropriate solvent, usually acetone for the amides, acids and esters and water for the salts and sprayed onto the foliage at a given dosage per acre in a carrier volume of about 50 gallons per acre. Growth responses were subsequently observed. In one such test the compounds of Example 1, 20 and 22 were compared using eleven-day old potted wheat plants. The compounds were prepared for testing as follows:

(a) Example 1.One-half gram of 1-(4-chlorophenyl) 3 carboxy 4,6-dimethylpyrid-2-one was dissolved in 100 ml. of acetone.

(ib) Example 20.-One-half gram of l-(4-chlorophenyl) 3 carboxy 4,6-dimethylpyrid-2-one (1.8 millimoles) was dissolved in 18 ml. of 0.1 N sodium hydroxide and the solution diluted with water to a volume of (c) Example 22.One-half gram of 1-(4-chlorophenyl) 3 carboxy 4,6-dimethylpyrid-2-one (1.8 millimoles) was dissolved in 15.3 ml. of 0.1177 N dimethylamine solution and the solution diluted to a volume of 100 ml.

The above solutions were sprayed onto the potted plants using a calibrated sprayer at such a rate as to deliver 2 lbs. per acre. The solutions were appropriately diluted for lower rates. Two months after treatment the percent inhibition as compared to control plants was measured. Table VII gives the results:

In seed treatment tests an aqueous solution or suspension of the test compound was prepared and diluted to various percent concentrations. Seeds were then immersed in these preparations for about 20 hours after which they were washed with water, planted in untreated soil, and the germination and growth subsequently observed.

In one such greenhouse test the sodium salt of 1-(4- chlorophenyl) 3 carboxy 4,6-dimethylpyrid-2-one (Example 20) was dissolved in water to give a series of concentrations varying from 0.03% to 3%. Seeds of barley, oats and wheat were treated with these solutions as indicated above and planted. Four weeks after planting the percent inhibition was determined. A 100% inhibition indicates that the seeds did not germinate or that no plants appeared. Table VIII gives the results:

Table IX gives plant responses obtained with 1-(4-chlorophenyl) 3 carboxy-4,6-dimethylpyrid-Z-one (Example 1) on a variety of plants by either the soil drench or foliar application method. These results are typical of the other compounds of this invention.

TABLE IX Typical Plant Responses Obtained with Example 1 Dosage Range Plant Species Response Observed 1 (lb./A)

Apple (seedlings) (Malua sylvestris) Stem (high dosage). Leaf epinasty 1-20 Barley (Hordeum vulgare) Stem. Seed. Initiation of flowering delayed 0. -3

(higher dosages). Barnyardgrass (Echinochloa crusgalli)--- Stem (slightly). Seed 1-10 Beans (dwarf) (Phaseolus vulgaris) Seseid. Nplmber oi bean pods increased. Malforma- M6-20 on o eaves. Coeklebur (zanthium penaylvanicum) Stem (high dosage). Malformation of burs 1-20 Corn (Zea maize) Stem (slightly) 0. 5-10 Cotton (Gossy'piu'm herbaceum) Stem (higher dosages) 0. 5-8 Cucumber (Cucumis sativus) Seed. Cucumber fruit i te 0. 5-4 Eggplant (Solanum melo'nga) Plants transplanted 2 weeks before treatment 0. 5-4

were dead or retarded.

Flax (Limt'm usitatisslum) Stem (slightly). Seed 0. 5-4 Grape (seedlings) (Vitis vinifera) Stem. Leaf epinasty (high dosage) 2-20 Mimosa (seedlings) (Acacia aTInfltll) Stem 8 Nutgrass (Cyperus esculentus) Stem (slightly) 5 Oats (Avena saliva Stem. Seed. Number and weight of heads in- 0. 75-3 increased.

' TABLE IX-Continued Dosage Range Plant Species Response Observed (1b./A)

Peach seedlln s Przmus prrsica) Stem (slightly) 1-8 Pigwee d (Ama r nihus retroflezus) Stem. Seed (higher dosages). Length of flower 1-10 heads decreased. Rice (On 2a satiau) Stem. Broader leaves 0. -8 Rye (Secale cereale) Stem. Seed 5 Safllower (Cartham'us tinctorma do 0. 5-4 Soybeans (Glycine max)... Stem (slightly). Seed I 0.5-4 Squash (Curcurbz'ta pepo) Segd. Nurrber of squash fruit increased but size 0. 5-4

ecrease Sugar beets (Beta vulgarity) Decreaed foliage weight and increased beet 0. 5-8

welg Tomato (Lycopersicum esculentum) Flowering prolonged. Fruit setting and develop- 0. 5-4

ment delayed. Turf grasses Stem 1-10 Wheat (Triticum vulaure) Stem. Seed (higher dosages). Plants had shorter, liethicker stems and shorter, broader and thicker leaves.

l Stem=Stom elongation inhibited. Seed= Seed formation inhibited.

In similar test, by foliar application, no appreciable growth inhibition was observed on carrot (Daucus carota), chrysanthemum (Chrysanthemum spp.), radish (Raphanus sativus), sunflower (Helianzhus ann'us) and turnip (Brassica rapa).

When the compounds of this invention are applied to plants or to the habitat of plants, they give a growth regulating response in the daosage range of about 0.01 to 30 pounds per acre (0.011 to 33 kilos per hectare). At the higher dosages, herbicidal responses may be manifested. Depending on the type of response desired the mount will vary with the plant species to be treated. Generally the preferred range is from 0.05 to 15 pounds per acre. Seeds may be treated with the compounds themselves or with any concentration of a solution or formulation of them.

The compounds of this invention may be employed as plant growth response agents either individually or as a mixture of two or more of them. They also may be used in combination with other plant growth regulatory compounds such as maleic hydrazide, succinic acid 2,2-dimethylhyrazide, choline and its salts, (2-chloroethyl)trimethylamrnonium chloride, triiodobenzoic acid, tributyl-2, 4-dicholrobenzylphosphonium chloride, polymeric N- vinyl-2-oxazolidinones, tri(dimethylaminoethyl) phosphate and its salts, and N-dimethylamino-1,2,3,'6-tetrahydrophthalamic acid and its salts. The compounds of this invention may also be combined with a herbicide for use on plants which are not sensitive to the herbicide at weed controlling rates. For example, they may be combined with 2,4-D for use on monocotyledonous plants such as cereals and turf grasses, with 3',4-dichloropropionanilide for use on rice or with 2,4dichlorophenyl-4-nitrophenyl ether for use on rice and other cereals.

The compounds of this invention may be applied in liquid carriers. One preferred group of the compounds are the water soluble salts in which case Water is the preferred carrier. Nonphytotoxic organic solvents such as ketones, alcohols, glycols, dimethylformamide and dimethyl sulfoxide may be employed. If desired a surfactant such as a Wetting agent may also be used and this usually constitutes a minor part (in general less than 10%) of the solution or formulation. The surface active agents may be anionic, cationic or non-ionic. For the water-soluble salts cationic and nonionic surfactants are preferred. Commonly used surfactants are well-known in the art and may be found in John W. McCutcheons publication Detergents and Emulsifiers, 1967 Annual, John W. McCutcheon Inc., Morristown, New Jersey.

The compounds of this invention may be formulated in various ways as for example e-mulsifiable concentrates, wettable powders, dusts, granules and pellets. Usually for application to the plant or plant parts or the plant habitat,

the formulations are extended with a suitable carrier. Emulsifiable concentrates are most usually extended with a liquid carrier such as water and dusts; granules and pellets are most usually extended with a solid carrier such as mineral clays.

Emulsifiable concentrates may be made by dissolving the compounds in an organic solvent and adding one or more solvent-soluble emulsifying agent. Suitable solvents are usually water-immiscible and may be found in the hydrocarbon, chlorinated hydrocarbon, ketone, ester, alcohol and amide classes of organic solvents.

Wettable powders may be made by incorporating the compounds in an inert, finely divided solid carrier along with a surfactant which :may be one or more emulsifying, wetting, dispersing or spreading agents or blends of these. Suitable carriers may be found in the classes of clays, silicates, silicas, limes, carbonates and organic carriers.

Solid compositions in the form of dusts may be made by compounding the compounds of this invention with inert carriers conventionally employed for the manufacture of pesticidal dusts for agricultural use, such as tales, finely particled clays, pyrophyllite, diatomaceous earth, magnesium carbonate or wood or walnut shell flours.

Granular or pelletized formulations may be made by incorporating the comopunds into granular or pelletized forms of agronomically acceptable carriers such asgranular clays, vermiculite, charcoal, ground corn cobs or bran.

Representative compounds of this invention have shown fungicidal activity. For example, the compound of Example 1 has given control of bean powdery mildew (Erisiphe polygoni) and the compounds of Examples 2, 5 and 16 given good control of tomato late blight (Phytophthora infestans).

The growth regulatory action of the compounds of the present invention may be advantageously employed in various ways. The production of shorter and thicker stems in cereal grains reduces the tendency toward lodging. Turf grasses may be maintained at a low height and the necessity for frequent mowing alleviated. The plant growth on embankments, such as roadsides, may be controlled to prevent erosion and at the same time maintain its aesthetic value. There may be an advantage in producing a dormant period in certain plants. The control of flowering and fruiting may be advantageous in the production of seedless fruit and for hybridization. Delaying the vegetative process or altering the time of flowering and fruiting may result in more advantageous harvest dates or increased fiower, fruit and/ or seed production. The chemical pruning of trees, shrubs, ornamentals and nursery stock may be beneficial. Other applications of the compounds of the present invention will suggest themselves to those skilled in the art of agriculture and horticulture.

1 7 We claim: 1. A compound of the formula wherein X is selected from the group consisting of amino, fluoro,

chloro, bromo, iodo, methyl, methoxy and nitro and X is selected from the group consisting of fiuoro, chloro, bromo, iodo, methyl and methoxy,

References Cited UNITED STATES PATENTS 3,144,388 8/1964 Kuhnis et a1. 260-294.9

HENRY R. J ILES, Primary Examiner A. L. ROTMAN, Assistant Examiner US. Cl. X.R. 

